This project focuses on the development of new vaccines for protection against mucosal infections, including herpes simplex virus type 2, the major cause of genital herpes infections. Novel vaccine approaches will be established with model antigens and applied to the development of a vaccine that will provide primary protection against mucosal infection with virulent HSV- 2. These will include the cloning and expression of viral genes in vectors for delivery directly to the mucosal immune system, the delivery of candidate naked DNA vaccine constructs to systemic and mucosal sites with novel adjuvants. The work involves cloning candidate viral genes into appropriate vectors, immunizing mice and/or guinea pigs with vaccine candidates, and testing for vaccine efficacy following experimental HSV-2 infections. Immunologic correlates of protection will also be evaluated using standard immunologic assays for antibodies, cytokine production, cell proliferation, and induction of cytotoxic T lymphocytes.